Abstract Alzheimer?s disease (AD) is an irreversible neurodegenerative disease and the most common cause of dementia in elderly adults. Drug development for AD has been slow so far, in part due to the inability of detecting AD lesions in the brain regions that degenerate first in the early stages of the disease. The progression of AD has been strongly linked to the accumulation of neurofibrillary tangles (NFT), which first appear in the locus coeruleus and then spread to the transentorhinal cortex and finally to the neo-cortex. With the advent of selective tau tracers, NFT distributions can now be characterized in vivo by Positron Emission Tomography (PET). For the newly developed 18F-MK-6240 tau tracer, higher uptakes were observed in medial temporal and neocortical brain regions in AD patients as well as non-specific uptake in the meninges. Though the SAVANT will offer unparalleled spatial resolution performance for a human scanner, quantitative accuracy and detection precision of NFT distributions will still be impacted by partial volume effects. It is thus clear that improvements in resolution are needed to extract the pathophysiological information present in a 18F-MK-6240 scan and allow detection of early NFTs associated with very prodromal AD. The goal of this administrative supplement is to develop, validate and optimize Bayesian reconstruction methodology leveraging super- resolution principles to enable detection of early NFTs in the regions at the origin of tau pathology in AD. The resulting improvement in image quality has the potential to significantly improve very early AD staging, providing new opportunities to assess anti-tau therapies and to optimize selection of participants for clinical trials.